This invention relates to novel organic arsenic compounds for treating tumor cells and which are particularly effective for inducing apoptosis in leukemia and breast tumor cells.
Cancer is a major disease that continues as one of the leading causes of death at any age. In the United States alone, it is anticipated that more than a half a million Americans will die of cancer in 1999. Currently, radiotherapy and chemotherapy are two important methods used in the treatment of cancer.
Considerable efforts are underway to develop new chemotherapeutic agents for more potent and specific anti-cancer therapy, presenting effective and efficient cytotoxicity against tumor cells, with minimal interference with normal cell function. Accordingly, there is an urgent need for the development and analysis of novel, effective anti-cancer agents.
New organic arsenic acid substituted cytotoxic agents with potent anti-tumor activity against cancer cells have been synthesized and examined for their effect on human leukemic cells and breast cancer cells. The compounds were found to exhibit potent cytotoxic activity, particularly against human breast cancer and leukemic cell lines, including primary leukemia cells, at micromolar concentrations.
Accordingly, the present invention includes novel compounds and compositions having potent cytotoxic activity. The present invention also includes methods for treating tumors by administering to a subject an anti-tumor effective amount of a compound of the invention. Compositions of the invention contain an effective or inhibitory amount of a organic arsenic acid substituted compound. The compounds of the invention include those having the following formula: 
where R is 
R1 is selected from a group consisting of H, NR3R4, SR3 and OR3, in which R3 and R4 are each independently hydrogen or a C1-C4 alkyl group. X is N or C. R2 is selected from the group consisting of H, NR3R4, SR3, OR3, and a group capable of bonding with X, when X is C, to form a fused aromatic or 5- or 6-membered heteroaromatic ring, or a pharmaceutically acceptable salt thereof.